The Possible Role of Prescribing Medications, Including Central Nervous System Drugs, in Contributing to Male-Factor Infertility (MFI): Assessment of the Food and Drug Administration (FDA) Pharmacovigilance Database.

BACKGROUND: A wide range of medications may have a possible role in the development of male-factor infertility (MFI), including various antineoplastic agents, testosterone/anabolic steroids, immunosuppressive drugs/immunomodulators, glucocorticosteroids, non-steroidal anti-inflammatory drugs, opiates, antiandrogenic drugs/5-alpha-reductase inhibitors, various antibiotics, antidepressants, antipsychotics, antiepileptic agents and others. We aimed at investigating this issue from a pharmacovigilance-based perspective. METHODS: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the drugs associated the most with MFI individual reports. Only those drugs being associated with more than 10 MFI reports were considered for the disproportionality analysis. Proportional Reporting Ratios (PRRs) and their confidence intervals were computed for all the drugs identified in this way in January 2023. Secondary, 'unmasking', dataset analyses were carried out as well. RESULTS: Out of the whole database, 955 MFI reports were identified, 408 (42.7%) of which were associated with 20 medications, which had more than 10 reports each. Within this group, finasteride, testosterone, valproate, diethylstilbestrol, mechloretamine, verapamil, lovastatin and nifedipine showed significant levels of actual disproportionate reporting. Out of these, and before unmasking, the highest PRR values were identified for finasteride, diethylstilbestrol and mechloretamine, respectively, with values of 16.0 (12.7-20.3), 14.3 (9.1-22.4) and 58.7 (36.3-95.9). CONCLUSIONS: A variety of several medications, a number of which were already supposed to be potentially linked with MFI based on the existing evidence, were associated with significant PRR levels for MFI in this analysis. A number of agents which were previously hypothesized to be associated with MFI were not represented in this analysis, suggesting that drug-induced MFI is likely under-reported to regulatory agencies. Reproductive medicine specialists should put more effort into the detection and reporting of these adverse drug reactions.

Medications mostly associated with priapism events: assessment of the 2015-2020 Food and Drug Administration (FDA) pharmacovigilance database entries.

A range of drugs have a direct role in triggering ischaemic priapism. We aimed at identifying: a) which medications are associated with most priapism-reports; and, b) within these medications, comparing their potential to elicit priapism through a disproportionality analysis. The FDA Adverse Event Reporting System (FAERS) database was queried to identify those drugs associated the most with priapism reports over the last 5 years. Only those drugs being associated with a minimum of 30 priapism reports were considered. The Proportional Reporting Ratios (PRRs), and their 95% confidence intervals were computed. Out of the whole 2015-2020 database, 1233 priapism reports were identified, 933 of which (75.7%) were associated with 11 medications with a minimum of 30 priapism-reports each. Trazodone, olanzapine and tadalafil showed levels of disproportionate reporting, with a PRR of 9.04 (CI95%: 7.73-10.58), 1.55 (CI95%: 1.27-1.89), and 1.42 (CI95%: 1.10-1.43), respectively. Most (57.5%) of the reports associated with the phosphodiesterase type 5 inhibitors (PDE5Is) were related with concomitant priapism-eliciting drugs taken at the same time and/or inappropriate intake/excessive dosage. Patients taking trazodone and/or antipsychotics need to be aware of the priapism-risk; awareness among prescribers would help in reducing priapism-related detrimental sequelae; PDE5I-intake is not responsible for priapism by itself, when appropriate medical supervision is provided.

Multiparametric Magnetic Resonance Imaging as a Noninvasive Assessment of Tumor Response to Neoadjuvant Pembrolizumab in Muscle-invasive Bladder Cancer: Preliminary Findings from the PURE-01 Study.

BACKGROUND: In the PURE-01 study, pembrolizumab was given preoperatively before radical cystectomy in clinical T2-4aN0M0 patients. An accurate clinical response assessment may be useful for developing new perioperative strategies in these patients. OBJECTIVE: To evaluate the association between bladder multiparametric magnetic resonance imaging (mpMRI) findings after pembrolizumab and the pathological complete response (CR; pT0). DESIGN, SETTING, AND PARTICIPANTS: Patients were staged using bladder mpMRI whereby radiologists were asked to characterize the following parameters: residual disease at T1- and T2-weighted images (step 1: yes/no), presence of hyperintense spots within the bladder wall on diffusion-weighted imaging (step 2: yes/no), and presence of pathological contrast enhancement (step 3: yes/no), before and after three cycles of pembrolizumab. Examinations were internally assessed by two senior radiologists and externally evaluated by a third senior radiologist. INTERVENTION: To evaluate bladder tumor response after neoadjuvant pembrolizumab, mpMRI was used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary objective was to predict the pT0 after neoadjuvant pembrolizumab by relying on the mpMRI findings. Cohen's kappa statistics was used to assess interobserver variability. Univariable analyses for pT0 were performed including internal and external post-therapy mpMRI steps. RESULTS AND LIMITATIONS: From February 2017 to October 2018, 82 patients (164 total mpMRI assessments) were analyzed. The agreement between the internal and external mpMRI assessments after therapy was acceptable (κ values ranging from 0.5 to 0.76). Each mpMRI step was significantly associated with pT0 in both internal and external assessments. In patients with CR/no evidence of residual disease (NED) in all internally evaluated mpMRI steps (N = 37), the pT0 was seen in 23 (62%), compared with 19 of 26 externally evaluated NED patients (73%). CONCLUSIONS: In post-pembrolizumab muscle-invasive bladder cancer, mpMRI sequence assessment had acceptable interobserver variability and represented the basis for the proposal of a radiological CR/NED status definition predicting the pT0 response to pembrolizumab. After validation of these findings with external datasets, we propose this tool for developing bladder-sparing immunotherapy maintenance therapies. PATIENT SUMMARY: Assessment of the extent of disease in patients with muscle-invasive bladder cancer using conventional imaging yields serious limitations. In the PURE-01 study, we evaluated the potential of bladder multiparametric magnetic resonance imaging (MRI) to predict the pathological complete response to neoadjuvant pembrolizumab. After validation with larger datasets, the proposed stepwise assessment incorporating multiparametric MRI sequences will be used at our center to develop bladder-sparing approaches in future studies.

Holmium laser enucleation of the prostate and holmium laser ablation of the prostate: indications and outcome.

PURPOSE OF REVIEW: Holmium laser enucleation of the prostate (HoLEP) has been proposed as an alternative to transurethral resection of the prostate and to open prostatectomy for patients with lower urinary tract symptoms because of large benign prostatic enlargement. The aim of this review is to critically analyze currently available evidence-based reports regarding HoLEP, with particular interest in long-term follow-up results. RECENT FINDINGS: The use of holmium laser for the treatment of benign prostatic hyperplasia was first reported in 1996. HoLEP seems to represent a valid alternative to both transurethral resection of the prostate and open prostatectomy, with valid long-term functional results, a low rate of short-term and long-term complications, and very low rates of reintervention. SUMMARY: HoLEP represents a valid alternative to both transurethral resection of the prostate and open prostatectomy for treatment of patients suffering from lower urinary tract symptoms due to benign prostatic enlargement. The recently published long-term follow-up data demonstrate the durability of functional results. HoLEP can be offered as the size-independent gold standard treatment of patients with lower urinary tract symptoms because of benign prostatic enlargement.

Health-insurance status is a determinant of the stage at presentation and of cancer control in European men treated with radical prostatectomy for clinically localized prostate cancer.

OBJECTIVE: To determine whether health-insurance status might result in more localized stage at presentation, more favourable stage at surgery and in a lower rate of biochemical recurrence (BCR), in patients diagnosed with prostate cancer and treated with radical prostatectomy (RP), as despite uninhibited access to healthcare, private and public health insurance are available in most European countries. PATIENTS AND METHODS: In all, 4442 consecutive men had RP in two large European centres, of whom 2372 had public and 2070 had private health insurance. The groups were compared for several variables according to insurance status (private vs public). Means and proportions tests were complemented with logistic regression or Kaplan-Meier analyses. RESULTS: Serum prostate-specific antigen level (P < 0.001), clinical stage (P < 0.001), pathological Gleason sum (P = 0.02), positive surgical margin rate (18.4% vs 25.4%, P < 0.001), extracapsular extension rate (17.7% vs 20.0%, P = 0.047) and seminal vesicle invasion rate (9.6% vs 11.6%, P = 0.04) were more favourable in privately insured patients. Conversely, the rate of lymph-node involvement was higher in those with private than public insurance (4.4% vs 3.3%, P = 0.045). In univariate analyses addressing pathological variables, private insurance was invariably protective (all P < 0.05). The Kaplan-Meier analyses showed that privately insured patients had a lower rate of BCR after RP (log-rank P = 0.017). CONCLUSION: Despite uninhibited access to healthcare, insurance status represents a rate-limiting variable, which affects stage at presentation and the outcome of cancer control.